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经血管外膜氯化钙和弹性蛋白酶渗透建立的小鼠腹主动脉瘤模型。

A Mouse Abdominal Aortic Aneurysm Model by Periadventitial Calcium Chloride and Elastase Infiltration.

机构信息

Division of Vascular Surgery, Department of General Surgery, West China Hospital, Sichuan University.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University.

出版信息

J Vis Exp. 2024 Aug 2(210). doi: 10.3791/66674.

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high mortality rates. It is characterized by the permanent dilation of the abdominal aorta with at least a 50% increase in arterial diameter. Various animal models of AAA have been introduced to mimic the pathophysiological changes and study the underlying mechanisms of AAA. Among these models, the calcium chloride (CaCl2)- and elastase-induced AAA models are commonly used in mice. However, these methods have certain limitations. Traditional intraluminal porcine pancreatic elastase (PPE) perfusion is associated with high technical difficulty and a high rupture rate, while periadventitial administration of PPE yields inconsistent results. In addition, the CaCl2-induced AAA model lacks human AAA features, such as atherothrombosis and aneurysm rupture. Therefore, the combined application of CaCl2 and PPE has been proposed as an approach to enhance success rates and induce greater diameter increases in AAA animal models. This manuscript presents a comprehensive protocol for establishing a mouse AAA model through periaortic infiltration of PPE and CaCl2 in the infrarenal segment of the abdominal aorta. By following this protocol, we can achieve an AAA formation rate of approximately 90% with technical simplicity and reproducibility. Further ultrasound and histological experiments confirm that this model effectively replicates the morphological and pathological changes observed in human AAA.

摘要

腹主动脉瘤(AAA)是一种危及生命的疾病,死亡率很高。其特征是腹主动脉永久性扩张,动脉直径至少增加 50%。已经引入了各种 AAA 的动物模型来模拟病理生理变化并研究 AAA 的潜在机制。在这些模型中,常用氯化钙(CaCl2)和弹性蛋白酶诱导的 AAA 模型在小鼠中进行研究。然而,这些方法存在一定的局限性。传统的腔内猪胰腺弹性蛋白酶(PPE)灌注具有较高的技术难度和较高的破裂率,而 PPE 的外膜下给药则产生不一致的结果。此外,CaCl2 诱导的 AAA 模型缺乏人类 AAA 的特征,如动脉粥样硬化和动脉瘤破裂。因此,已经提出了 CaCl2 和 PPE 的联合应用,以提高 AAA 动物模型的成功率并诱导更大的直径增加。本文提出了一种通过在腹主动脉肾下段进行 PPE 和 CaCl2 的主动脉周围渗透来建立小鼠 AAA 模型的综合方案。按照此方案,我们可以实现约 90%的 AAA 形成率,具有技术简单性和可重复性。进一步的超声和组织学实验证实,该模型有效地复制了人类 AAA 中观察到的形态和病理变化。

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